JP2009541236A5

JP2009541236A5 -

Info

Publication number: JP2009541236A5
Application number: JP2009515748A
Authority: JP
Filing date: 2007-06-15
Publication date: 2010-07-29

Claims

(I) at least one heterologous nucleotide sequence expressing in vivo at least one heterologous nucleotide sequence, in particular a heterologous nucleotide sequence encoding an antigen, and (ii) at least one 1H-imidazo [4,5-c ] A recombinant virus vaccine comprising a quinolin-4-amine derivative.

(I) a container containing at least one heterologous nucleotide sequence expressing in vivo at least one heterologous nucleotide sequence, in particular a heterologous nucleotide sequence encoding an antigen, and (ii) at least one 1H-imidazo [4 , 5-c] a vaccination kit comprising a container containing a quinolin-4-amine derivative.

The recombinant virus vaccine according to claim 1 or the kit according to claim 2, wherein the poxvirus vector is a highly attenuated vaccinia virus strain.

The recombinant virus vaccine according to claim 3, wherein the highly attenuated vaccinia virus strain is a highly attenuated vaccinia virus strain derived from a Copenhagen strain or a Weiss strain.

The 1H-imidazo [4,5-c] quinolin-4-amine-derivative is represented by the following general formulas I to V:
I-

[Where:
R ₁₁ is selected from the group consisting of linear or branched alkyl, hydroxyalkyl, acyloxyalkyl, benzyl, (phenyl) ethyl and phenyl, wherein the benzyl, (phenyl) ethyl or phenyl substituent is optionally selected from its benzene On the ring, it may be substituted with one or two moieties independently selected from the group consisting of a C _1-4 alkyl moiety, a C _1-4 alkoxy moiety and a halogen (provided that the benzene ring is 2 When substituted with two such moieties, both moieties contain no more than 6 carbon atoms);
R ₂₁ is selected from the group consisting of hydrogen, C _1-8 alkyl moiety, benzyl, (phenyl) ethyl and phenyl, wherein the benzyl, (phenyl) ethyl or phenyl substituent is optionally on the benzene ring, _May be substituted with 1 or 2 moieties independently selected from the group consisting of a C _1-4 alkyl moiety, a C _1-4 alkoxy moiety and a halogen (provided that the benzene ring has two such moieties; in the case of substitution, the moiety containing up to 6 carbon atoms combined); and each R ₁ is hydrogen, C _1-4 alkoxy moieties, the group consisting of halogen and C _{1 - 4} alkyl moiety And n is an integer of 0 to 2 (provided that when n is 2, the R ₁ group together contains 6 or less carbon atoms)]
Or a compound, analog, solvate or salt thereof as defined by
II-

[Where:
R ₁₂ is a straight chain or branched C _2-10 alkenyl and a substituted straight chain or branched C _2-10 alkenyl, wherein the substituent is a straight chain or branched C _1-4 alkyl moiety and C _{3 -6} selected from the group consisting of cycloalkyl moiety); and is selected from the group consisting of C _{3 -6} cycloalkyl moiety substituted by a straight or branched C _{1 - 4} alkyl moiety;
R ₂₂ is selected from the group consisting of hydrogen, a linear or branched C _1-8 alkyl moiety, benzyl, (phenyl) ethyl and phenyl, wherein the benzyl, (phenyl) ethyl or phenyl substituent is optionally Substituted on the benzene ring with 1 or 2 moieties independently selected from the group consisting of a linear or branched C _1-4 alkyl moiety, a linear or branched C _1-4 alkoxy moiety and a halogen. (Provided that when the benzene ring is substituted with two such moieties, the moieties together contain no more than 6 carbon atoms); and each R ₂ may be linear or branched C _1-4 alkoxy moiety is selected independently from the group consisting of halogen and straight-chain or branched C _{1 - 4} alkyl moiety, n is an integer of 0 to 2 (where, n is 2 If, in the R ₂ groups containing up to 6 carbon atoms combined)
Or a compound, analog, solvate or salt thereof as defined by
III-

[Where:
R ₂₃ is selected from the group consisting of hydrogen, a linear or branched C _1-8 alkyl moiety, benzyl, (phenyl) ethyl and phenyl, wherein the benzyl, (phenyl) ethyl or phenyl substituent is optionally Substituted on the benzene ring with 1 or 2 moieties independently selected from the group consisting of a linear or branched C _1-4 alkyl moiety, a linear or branched C _1-4 alkoxy moiety and a halogen. (Provided that if the benzene ring is substituted with two such moieties, the moieties together contain no more than 6 carbon atoms); and each R ₃ may be linear or branched C _1-4 alkoxy moiety is selected independently from the group consisting of halogen and straight-chain or branched C _{1 - 4} alkyl moiety, n is an integer of 0 to 2 (where, n is 2 If, in the R ₃ groups containing up to 6 carbon atoms combined)
Or a compound, analog, solvate or salt thereof as defined by
IV-

[Where:
R ₁₄ is _-CHR 34 _{R 44,} _{wherein, R 44} is hydrogen or a carbon - is carbon bond, provided _that when _{R 44} is _{hydrogen, R 34} is _{C 1-4} alkoxy moiety, C _{1 - 4} A hydroxyalkoxy moiety, a C _2-10 1-alkynyl moiety, a tetrahydropyranyl, an alkoxyalkyl, wherein the alkoxy moiety contains 1 to 4 carbon atoms, and the alkyl moiety contains 1 to 4 carbon atoms ), 2-, 3-, or 4-pyridyl, but when R ₄₄ is a carbon-carbon bond, R ₄₄ and R ₃₄ are taken together to form a hydroxy and C _1-4 hydroxyalkyl moiety. Forming a tetrahydrofuranyl group optionally substituted with one or more substituents independently selected from the group consisting of:
R ₂₄ is selected from the group consisting of hydrogen, C _1-4 alkyl, phenyl, which phenyl is optionally linear or branched C _1-4 alkyl moiety, linear or branched C _1-4 alkoxy moiety and halogen Optionally substituted with 1 or 2 moieties independently selected from the group consisting of: and R ₄ is hydrogen, linear or branched C _1-4 alkoxy moiety, halogen and linear or branched Selected from the group consisting of C _1-4 alkyl moieties]
Or a compound, analog, solvate or salt thereof as defined by
V-

[Where:
R ₁₅ is hydrogen; straight or branched C _{1 -10} alkyl moiety and substituted straight chain or branched _{C 1-10} alkyl moiety (wherein, the substituents C _{3 -6} cycloalkyl and straight or Selected from the group consisting of C _3-6 cycloalkyl substituted with a branched C _1-4 alkyl moiety); linear or branched C _2-10 alkenyl and substituted linear or branched C _2-10 alkenyl portion (wherein the substituents are selected from the group consisting of C _{3 -6} cycloalkyl substituted with C _3-6 cycloalkyl and straight or branched C _1-4 alkyl moiety); C _1- (wherein the alkoxy moiety contains 1 to about 4 carbon atoms, the alkyl moiety comprises 1 to about 6 carbon atoms) alkoxyalkyl; ₆ hydroxyalkyl acyloxyalkyl (here, The acyloxy moiety is alkanoyloxy or benzoyloxy of 2 to about 4 carbon atoms, the alkyl moiety containing 1 to about 6 carbon atoms); benzyl; (phenyl) ethyl; and phenyl; (the benzyl, (Phenyl) ethyl or phenyl substituent is optionally 1 or 2 moieties independently selected from the group consisting of C _1-4 alkyl moiety, C _1-4 alkoxy moiety and halogen on the benzene ring Wherein, when the benzene ring is substituted with two of the moieties, the moieties are selected from the group consisting of up to 6 carbon atoms;
R ₂₅ is

{Where,
And R _35, C 1 _{- 4} alkoxy moiety, alkoxyalkyl (wherein the alkoxy moiety contains 1 to about 4 carbon atoms, the alkyl moiety comprises from 1 to about 4 carbon atoms); C ₁ (wherein the alkyl group contains 1 to about 4 carbon atoms) alkyl amide; _-4 haloalkyl moiety amino; C _1-4 alkyl or C _{1 - 4} amino substituted by hydroxyalkyl; azido; C Selected from the group consisting of _1-4 alkylthio;
R ₅₅ and _{R 45} are _{hydrogen, C 1-4} alkyl moiety, and phenyl (wherein the phenyl may optionally linear or branched C _{1 - 4} alkyl moiety, linear or branched _{C 1-4} alkoxy moiety, and be independently selected from each other from the group consisting of may also) from the group consisting of halogen substituted one or two parts component chosen independently of one another}; and R ₅ is hydrogen , straight or branched C _1-4 alkoxy moiety is selected from the group consisting of halogen and straight-chain or branched C _{1 - 4} alkyl-containing moiety]
The recombinant virus vaccine or kit according to claim 1, which is a compound defined by the above, or an analog, solvate or salt thereof.

The 1H-imidazo [4,5-c] quinolin-4-amine derivative is a compound defined by the following general formula VI:

[Where:
Rt is selected from the group consisting of hydrogen, linear or branched C _1-4 alkoxy moiety, halogen and linear or branched C _1-4 alkyl;
Ru is 2-methylpropyl or 2-hydroxy-2-methylpropyl; and Rv is hydrogen, C _1-6 alkyl or alkoxyalkyl, wherein the alkoxy moiety contains 1 to about 4 carbon atoms; The alkyl moiety contains 1 to about 4 carbon atoms)]
Or the recombinant virus vaccine or kit as described in any one of Claims 1-4 which is an analog, a solvate, or a salt thereof.

The heterologous nucleotide sequence (i) encodes all or part of one or more of HPV-E1, E2, E3, E4, E5, E6, E7, E8, L1, and L2 antigens. A recombinant virus vaccine or kit according to claim 1.

(I) at least one recombinant viral vector expressing at least one heterologous nucleotide sequence encoding the antigen in vivo; and (ii) at least one 1H for use in enhancing an immune response to the antigen in a patient. A combination with an imidazo [4,5-c] quinolin-4-amine derivative, wherein the administration of the 1H-imidazo [4,5-c] quinolin-4-amine derivative comprises administering the recombinant viral vector; A combination that is performed independently of and prior to the second administration.

(I) at least one recombinant viral vector expressing at least one heterologous nucleotide sequence encoding the antigen in vivo; and (ii) at least one 1H for use in enhancing an immune response to the antigen in a patient. A combination with an imidazo [4,5-c] quinolin-4-amine derivative, wherein the administration of the 1H-imidazo [4,5-c] quinolin-4-amine derivative comprises administering the recombinant viral vector; A combination which is performed simultaneously with a second administration consisting of

(I) a container containing at least one recombinant viral vector expressing at least one heterologous nucleotide sequence encoding the antigen in vivo ; (ii) for use in enhancing an immune response against the antigen in a patient; In combination with a container containing at least one 1H-imidazo [4,5-c] quinolin-4-amine derivative , wherein the administration of the 1H-imidazo [4,5-c] quinolin-4-amine derivative comprises A combination performed simultaneously with a second administration comprising the administration of the recombinant viral vector

11. The combination according to any one of claims 8 to 10, wherein the recombinant viral vector that expresses at least one heterologous nucleotide sequence encoding an antigen in vivo is a recombinant poxvirus vector.

The heterologous nucleotide sequence (i) encodes all or part of one or more of HPV-E1, E2, E3, E4, E5, E6, E7, E8, L1, L2 antigens. A combination according to any one of the above.